Supporting Molecular Imaging:
Current cross-sectional MR and CT anatomically based imaging is becoming more sensitive but less specific as their ability to detect small lesions (e.g. in liver and lung) increases. More specific disease markers are required to enable further progression in the development of imaging technology and this is particularly relevant for cancer. Recent major investment in both Clinical and Academic Oncology Departments and by CRUK in the Cambridge Research Institute (CRI) is bringing fresh opportunities for new imaging technique development in support of translational oncology research. There is considerable clinical MR collaboration with the newly formed CRI Imaging Group which is developing an animal imaging department. Clinical collaboration aims to develop novel molecular imaging agents for tissue function and metabolism using conventional 1H based MR, 13C hyperpolarised methodologies as well as optical and novel PET radionuclide methods. There will be a focus on apoptosis and epithelial dysplasia with initial evaluation in mouse models and ex-vivo human tissues and translation of successful agents to human evaluation studies using clinical imaging systems. The initial funding for clinical MRI has been provided by CRUK and a local charity but additional NHS funding will allow expansion and enhancement of this collaboration. Through links with the Stanford University Molecular Imaging Program a joint educational program has been established to support training fellowships that could be linked to the CRUK CRI and the proposed CCI molecular imaging groups. A specific target of this work is in-vivo reporter gene imaging that can provide information not only on cell trafficking, but also on cellular function and survival. This should lead on to the use of molecular imaging in reparative medicine applications, e.g. neurogenesis (in the context of neural injury e.g. stroke, trauma, neurodegeneration, and neuroinflammation), as well as other applications to understand cancer biology and therapy.
Extend MRI Applications:
As life expectancy increases so is concern at the rapidly increasing population exposure to ionising radiation. We will extend the diagnostic role of conventional whole body MRI systems and perform studies to demonstrate where MR could eventually replace many more X-ray procedures. This will involve the development of user interfaces, in room control and display capabilities, and innovative sequence and application design. This will be a progression of our existing work on MR fluoroscopy techniques, gastro-intestinal (MR enteroclysis) and musculoskeletal systems (MR arthrography). Alongside this work we will continue to extend existing MR research techniques using 1H and 31P MRS for metabolic tumour profiling and investigate the potential benefit of new MR staging methods in guiding robotic prostate surgery and other forms of tumour therapy. We have patented a methodology that combines PET with MR data: this venture between the WBIC and the Cavendish laboratory is resolving the distribution of novel chemicals within the living brain.
Developing Robust Quantitative Imaging
We will develop and validate quantitative imaging methods for monitoring disease progress and the effects of therapeutic interventions in a wide range of specialties, particularly oncology, cardiology, gastroenterology, metabolic science and neuroscience. The aim will be to provide several generic robust quantitative measurements including: tissue perfusion parameters (e.g., brain perfusion in acute stroke), spatial enhancement patterns, T2 mapping, vascular bulk flow, fat distribution and tissue fat content.
Novel Imaging of the Neurologically Impaired
The refinement and development of imaging techniques for characterising carotid disease and stroke will continue with the aim of developing robust non-invasive imaging techniques to identify both patients at risk of stroke and those who respond to treatment. New imaging methods are helping to distinguish ‘safe’ from ‘unsafe’ atheroma and hence predicting the risk of a stroke, the need for preventive surgery and the determination of which treatments are safe and effective. The unique facilities of 3T MR and PET adjacent to the acutely ill patients in the Neurosciences Critical Care Unit provide exceptional research opportunities for Neurosurgery, Neurology, Psychiatry, Anaesthesiology and Radiology. We are developing new state-of-the-art real time fMRI including online methods of analysing the resulting data, particularly for studying those emerging from coma and with minimal consciousness. These will show what happens to the brain as patients emerge from coma; this should help predict outcome and the most appropriate form of rehabilitation. fMRI techniques will be used to further our understanding of attention, memory, speech, language, eating disorders and emotion. We will attempt to distinguish between the different types of dementia using morphometric imaging, functional imaging and neuropsychology. Novel analysis algorithms are being developed in order to better assess anatomical connections between brain structures and their impairment in disease or following trauma. We will assess brain viability in acute ischaemic stroke and determine the secondary changes, and their impact on functional recovery. We will assess how drugs interact with parts of the brain concerned with learning and higher mental function in order to increase understanding of mental illness and addiction. We will use fMRI to follow changes in brain organisation after focal injury and to see how neurorehabilitation modulates brain plasticity. We will continue to exploit these studies in association with the MRC funded Cambridge Cognition and Brain Sciences Unit and the MRC/Wellcome Trust funded Behavioural and Clinical Neurosciences Institute based in Experimental Psychology and the Brain Mapping Unit in Psychiatry. These facilities have been well used despite relatively little NHS R&D support to date and require considerable physics, data handling and computing support, as well as clinical infrastructure. The much needed improvement in the radiopharmaceuticals laboratory will underpin future research using novel PET ligands.
Defining New Roles for CT
Cambridge is well placed in collaboration with Papworth (recent installation of a 64 slice double tube CT system) to continue investigating the role of CT for cardiac and coronary imaging, extending the preliminary work based on existing 16 and 64 slice systems. This research will ultimately determine which patients can be safely managed with CT, thereby avoiding invasive coronary angiography. We will continue to evaluate the role of immediate CT in the triage of acute medical and surgical conditions (including trauma), especially assessing volume CT data manipulation. In addition we will exploit this volume imaging capability to develop new CT and PET/CT techniques for the detection and monitoring of early lung cancer in collaboration with Clinical Oncology.
